It has long been known that many photoluminescent materials exhibit substantial reductions in their luminescent intensities or luminescent decay lifetimes as a result of increases in the temperature of the material. These characteristics have been exploited in the development of various fiber optic temperature sensor probes (See Urbach, U.S. Pat. No. 2,551,650, Samulski, U.S. Pat. Nos. 4,437,772, 4,245,507, Quick U.S. Pat. No. 4,223,226, Wickersheim, et al., (Recent Advances in Optical Temperature Measurement, Industrial Research & Development, December, 1979), Sholes, et al., (Fluorescent Decay Thermometer with Biological Applications, Rev. Sci. Instrum., 51, 7 July , 1980), and Tekippe, U.S. Pat. No. 4,374,328.
For some luminescent materials, "quenching" (i.e., reductions in luminescent intensity) due to the presence of oxygen molecules (see Bergman, Rapid-response Atmospheric Oxygen Monitor based on Fluorescence Quenching, Nature 218, 396, Stevens, U.S. Pat. No. 3,612,866, Lubbers, U.S. Pat. Re. 31,879, Peterson U.S. Pat. No. 4,476,870, and Cox, "Detection of O.sub.2 by fluorescence quenching", Applied Optics/ 24, 14, 1985) has been exploited for the construction of fluorometric probes.
Further, the presence of the hydrogen ion can sensitively quench some luminescent materials (see Lubbers U.S. Pat. Re. 31,879, and Saari, et al., "pH sensor based on immobilized fluoresceinamine", Anal. Chem. 1982, 54, 821-3), as can a variety of other chemical quenching species, such that it is possible to measure the concentrations of such quenching species via "fluorometric sensors". (See Harte, U.S. Pat. No. 3,992,631).
Generally, it can be stated that fluorescence quenching (i.e., using reductions in intensity of emission of a photoluminescent material to measure concentration of a quenching species) is a well established methodolgy in analytical chemistry.
However, direct measurement of the photoluminescent lifetimes of those materials suitable or useful for assay of chemical species such as the oxygen molecule or hydrogen ion or other blood gasses has generally been reserved for the research laboratory, and such techniques have not been used in the field of fiber optic sensors which are placed in a remote environment. This has been true for several reasons: (1) The photoluminescent lifetimes of suitable materials is generally quite short. For instance, Lubbers teaches the use of Parylene Dibutyric Acid and Beta Methyl Umbelliferone; Cox, the use of 9, 10 Diphenyl Anthracene. Other examples are cited in the referenced prior art. The photoluminescent lifetime of such species is on the order of 10 nanoseconds, and generally with required excitation wavelengths in the ultraviolet. In order to accomplish lifetime measurements on such specie a large, expensive excitation light source has been required such as a gas ion laser with internal or external modulation capabilities in the nanosecond (Gigahertz) range. (2) Photosensor systems for detecting and analyzing such high speed luminescent decays whether by direct pulse contour analysis (see Lackowicz, Principles of Fluorescence Spectroscopy, Chapter 3, Plenum Press, New York 1983, and Gafni, et al., Analysis of Fluorescence Decay Curves by Means of the Laplace Transformation, Biophysical Journal, 15, 1975) or by analysis of the emitted luminescent response to a modulated excitation source (see Lackowicz, Chapter 3 & 4; Gratton, et al., A continuously Variable Frequency Cross-Correlation Phase Fluorometer with Picosecond Resolution, Biophysical Journal, 44, December, 1983; Lytle, et al., Spectroscopic Excitation Source with Variable Frequencies and Shapes of Modulation, Anal. Chem. 47, 3, 1975; Hauser, et al., Phase Fluorometer with a continuously variable frequency, Rev. Sci. Instrum., 46, 4, 1975, and Birks, et al., Phase and Modulation fluorometer, J. Sci. Instruments, 38, July, 1961) are again expensive and bulky, and subject to considerable detection errors as a result of minor changes in the pulse shape or modulation characteristic of the light source.
As a result of the foregoing size, sophistication, and expense of laboratory lifetime measurement apparatus, previous workers in the field of catheter-based fiber optic sensing systems for the detection of oxygen and other fluid components in the body have relied upon the measurement of quenching--i.e., the reduction in average luminescent intensity of the fluorometric sensor due to the presence of the quenching fluid component upon application of a precisely regulated, continuous source of excitation light. However, there are definite advantages to the measurement of luminescent lifetimes as opposed to quenching intensities in the field of catheterbased fiber optic sensors:
(1) Flexing of the catheter and fiber optic as normally occurs in catheter applications causes a reduction in quench/intensity which can be interpreted by the user as a change in the quencher concentration at the tip of the catheter. Lifetime measurement, which is not dependent on the absolute intensity of luminescence transmitted through the fiber optic light pipe, does not suffer from this drawback.
(2) A fiber optic sensor probe employing lifetime measurements could be easily disconnected and reconnected to a lifetime measurement apparatus without concern for recalibration of the apparatus due to chanes in the attenuation of the intervening fiber optic connector. This is a significant practical advantage in critically ill patients who undergo many tests and procedures.
(3) During operation, a fluorometric sensor normally suffers some reduction in luminescent intensity output due to photo-destruction of the luminescent material by the incident light source. This source "drift," in an intensity measurement system, can be interpreted by the user as an increase in quencher concentration at the tip of the catheter. Lifetime measurement systems do not suffer from "drift" due to slow photo-destruction or bleaching of the luminescent material since they are not sensitive to quench intensity variations.
In an article entitled "Phase fluorimetry with a variable duty cycle electrical phosphoroscope," Gruneis, et al., discloses a mechanically-chopped light source used in conjunction with a synchronized electrically gated photosensor to separate out and measure the decay curve of the relatively long-lived phosphorescence component of a luminescent material while eliminating strong short term interference from the light source and from an accompanying fluorescent emitted component from the material. The area under the remaining long term decay curve is integrated and used with a single-exponent mathematical model to indirectly estimate phosphorescent lifetime.
Fisher and Winefordner (Pulsed Source-Time Resolved Phosphorimetry, Analytical Chemistry, 44, 6, 1972) disclose phosphorimeters wherein time-delayed, gated detectors integrate the phosphorescent response to a pulsed light source ot obtain an indication of the lifetime of organic phosphors.
James, et al. (Analysis and Preliminary Design of optical sensors for propulsion control, NTIS Report #N79-27975, U.S. Dept. Commerce, January, 1979) describes the construction of pulsed, luminescent, fiber optic temperature sensor wherein the time required for the sensor's luminescence to decay from a normalized initial intensity to a specified fraction thereof is measured and related to temperature.
Sholes (Fluorescent decay thermometer with biological applications, Rev. Sci. Instrum., 51 (7), 1980) excites the long-lived fluorescence of ruby with a short pulse of light and integrates precisely-timed portions of the resulting decay curve after a predetermined threshold point to develop a computation which is said to be related to the temperature of the sensor. Sholes specifically teaches against sampling of the decay curve because of problems with D.C. shift and noise in the amplifier/detector and variations in the light source intensity.
Samulski (U.S. Pat. No. 4,245,507) proposes a fiber optic probe for temperature sensing in the human body and recognizes that the sensor's luminescent output could be analyzed via pulse decay or phase shift techniques, but fails to describe how such an analysis system might be constructed.
In pending British patent application No. 2132348A, Demas, et al., describes a group of organometallic compounds suitable for use as fluorescent oxygen sensors when embedded in polymer matrixes. Demas discloses that these materials could be used in conjunction with intensity or lifetime analysis techniques for construction of a fiber optic oxygen sensor system for use inside the body. Demas has also described (see Luminescence Spectroscopy and Bimolecular Quenching, J. Chem. Ed., 52, 10, 1975; Luminescence Decay Times and Bimolecular Quenching, J. Chem. Ed., 53, 10, 1976, and Inexpensive Laser Luminescence Decay Time Apparatus, Anal. Chem., 48, 2, 1976) two decay time analysis systems which are said to be inexpensive means for measuring the lifetimes of the referenced organometallics or of other luminescent materials. The first system uses a flashlamp, and the second a pulsed-nitrogen laser to deliver a pulse of excitation light to the luminescent material, whereupon, the resulting luminescent decay is detected and analyzed by graphical methods using a storage oscilloscope.
Each of the foregoing prior art techniques has its own drawback and limitation with respect to construction of fiber optic temperature or fluid component sensors for use inside the body and in body fluids, and for an accessory lifetime measurement appartus.
The instruments of Gruenis, et al., and Fisher, et al. fairly represent the current state of the art in Time-Resolving Phosphorimeters, wherein the area under a phosphorescent decay curve of a phosphor material located in a sample compartment is integrated over a predetermined time interval following the extinction of an excitation lamp, whereupon the integral is related to the lifetime of the phosphor.
These laboratory instruments are incapable of measuring fluorescent decays--which are 1000 times or more faster than phosphorescent decays, and in fact the authors teach that it is an advantage that the instruments are insensitive to such faster fluorescent decays. In addition, such instruments are not constructed or proposed for use with fiber optic sensors placed in remote environments.
The signal analysis techniques of James, et al. and Quick, U.S. Pat. No. 4,223,226, in a fiber optic temperature sensor system, require the decay curve of a phosphor to decline to a preset threshold, whereupon a timer is started and then stopped when the decay further declines to a second predetermined threshold. However, since fluoescent decays are very fast, noisy phenomena, it is difficult if not impossible to measure such thresholds accurately. The temperature sensor system of Sholes similarily depends upon the on-line sensing of a preset threshold before curve integration can begin.
None of workers in the field of fiber optic temperature sensors have proposed that pulse decay-curve analysis techniques described in the prior art are suitable or usable for the development of oxygen or pH sensor probes.
The first apparatus reported by Demas uses a flashlamp with a relatively long and unpredictable decay characteristic. Demas' results with this device depend on tedious curve tracing and deconvolution techniques which result in considerable experimental errors. The second apparatus of Demas uses a nitrogen laser which is expensive and difficult to maintain. Results still depend on manual curve tracing, graphical analysis, and the services of an off-line computer.